Ion-selective electrodes (ISEs) are widely used to measure the concentration of ions in fluids. Such electrodes have been employed in a wide variety of potentiometric determinations including, for example, determination of the fluoride ion in drinking water and determination of various electrolytes in biological fluids. For example, ISEs are routinely used to determine sodium, calcium, magnesium, potassium, lithium and chloride ions in serum.
Generally, ion selective electrodes are composed of an ion selective membrane, an internal electrolyte solution and an internal reference electrode. An external reference electrode used in conjunction with the ion selective electrode is typically a metal/metal halide electrode such as Ag/AgCl. An ion selective electrode and an external reference electrode comprise a potentiometric cell assembly. Selective transfer of the ion of interest from the sample solution to the ion selective electrode membrane produces an electrical response. The mathematical expression which relates the potential difference across the membrane to the difference in activity is defined by the Nernst Equation, whereas the magnitude of the response is defined as sensitivity. The measured potential difference (ISE versus outer reference electrode potentials) is linearly dependent on the logarithm of the activity of a given ion in solution, and can be used to quantify the ion under investigation. If the membrane's sensitivity does not remain constant during repeated exposure to sample fluids, inaccurate or spurious measurements will be produced and the membrane electrode will have limited use life.
Ion selective electrode membranes are typically formed from a plasticized polymer matrix which contains an ionophore selective for the ion of interest. Many attempts have been made to determine chloride ion in fluid samples using chloride selective electrode membranes. A specific example of such a membrane consists of a polymer, such as polyvinylchloride, an ionophore or ion selective component such as a quaternary ammonium compound and a plasticizing agent for imparting ion motility to the membrane. Quaternary ammonium and phosphonium compounds are frequently employed as ionophores for chloride selective membrane electrodes. Examples of such compounds include tridodecylmethylammonium chloride and tetradodecylammonium chloride. Generally, such chloride selective components are chosen for their lipophilic properties which contribute to enhanced membrane life. Unfortunately, fluids in contact with the membrane can extract plasticizers and ionophores out of the membrane causing the sensitivity of the membrane to be compromised. This is particularly problematic when heparinized plasma samples are analyzed because heparin has been found to adversely affect the membrane. This adverse effect may be due to extraction of ionophore or contamination of the membrane surface with protein which severely limits the use life of the electrode. Use life of an electrode is generally defined as the amount of exposure required to cause the sensitivity to fall below 60% Nernstian.
Another requirement of a chloride selective electrode is that it has a minimal response to substances other than the analyte of interest. This characteristic is known as selectivity. Sample fluids often contain substances which interfere with the electrode membrane thereby producing a spurious electrical response. With respect to chloride selective membrane electrodes, a particularly difficult challenge is achieving high selectivity over ions like salicylates (in blood and urine) and/or other similar ions and maintaining this selectivity during repeated exposure of the electrode to interfering substances.
As is evident from the foregoing, degradation in the sensitivity and selectivity of a chloride selective membrane electrode as a result of repeated exposure to samples containing interfering substances, as well as the analyte of interest, remains a significant problem. In addition, extending the use life of chloride sensitive membrane electrodes by increasing the stability of membrane selectivity without adversely affecting the sensitivity presents significant challenges.